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PubMed This is a summary of 24 peer-reviewed journal articles Updated
Genetics

The Three Subtypes and Symptoms of CPT II Deficiency

At a Glance

CPT II deficiency has three main subtypes: myopathic, severe infantile, and lethal neonatal. The most common myopathic form causes muscle pain and dark urine after exercise, fasting, or illness. The rarer infantile and neonatal forms cause severe heart and liver complications early in life.

Carnitine Palmitoyltransferase II (CPT II) deficiency is a spectrum of conditions rather than a single experience. Because the body’s ability to use fat for fuel is impaired, symptoms typically appear when the body is under stress [1]. Generally, the earlier in life symptoms begin, the more severe the condition tends to be [2][3].

1. Myopathic Form (The Most Common)

The myopathic form is the most frequent and usually the least severe version of the condition. It primarily affects the skeletal muscles [1][4].

  • When it starts: Symptoms can begin anytime from childhood through adulthood [5][6].
  • Key Symptoms: The hallmark of this form is recurrent episodes of:
    • Myalgia: Intense muscle pain [7].
    • Muscle weakness: Feeling heavy or unable to move normally [5].
    • Rhabdomyolysis: A serious condition where muscle tissue breaks down and releases proteins into the blood [7].
    • Myoglobinuria: Dark-colored urine (often described as tea-colored or cola-colored), which is a sign that muscle protein is being filtered by the kidneys [8][9].

Common Triggers for the Myopathic Form

In the myopathic form, the “gate” that lets fat into the cells works well enough for everyday life but fails when demand is high. Specific triggers that can cause a muscle breakdown include:

  • Prolonged Exercise: Especially sustained activities like long-distance running or hiking [10][7].
  • Fasting: Going too long without eating, which forces the body to try and use fat for fuel [5][10].
  • Illness and Fever: Infections can increase the body’s metabolic rate. Some genetic variants like S113L may make the CPT II enzyme even less stable when body temperature rises [7][11][12].
  • Cold Exposure: Shivering or extreme cold can also trigger muscle breakdown [7].

2. Severe Infantile Form (Hepatocardiomuscular)

This form typically appears in the first year of life. It primarily affects the liver, heart, and muscles—hence the name “hepatocardiomuscular” [13].

  • When it starts: Usually between 6 and 24 months of age [13].
  • Key Symptoms: Infants may experience recurrent “metabolic crises” often triggered by common viral illnesses [14]. These crises can involve:
    • Liver dysfunction: Leading to low blood sugar and lethargy [15][16].
    • Cardiomyopathy: A weakening of the heart muscle that makes it harder to pump blood [13][17].
  • Risk: These episodes can be life-threatening and require immediate medical intervention to stabilize blood sugar and support the heart [18][13].

3. Lethal Neonatal Form (The Most Severe)

This is the rarest and most severe form of CPT II deficiency. It appears within the first few days of life and involves multiple organ systems [19][18].

  • When it starts: Within hours or days after birth [15].
  • Key Symptoms: Severe lethargy, seizures, icterus (jaundice or yellowing of the skin), and dangerously low blood sugar (hypoglycemia) [15][20].
  • Structural Involvement: This form is unique because it can cause physical changes in how organs develop before birth. These may include polycystic kidneys (cysts on the kidneys), cardiomegaly (an enlarged heart), and brain malformations such as polymicrogyria (extra folds in the brain) [21][22][23].

Understanding these forms and your genetic results helps families and doctors create a “safety net” by identifying early warning signs and avoiding the specific triggers that lead to crises [7][24].

Common questions in this guide

What is the most common form of CPT II deficiency?
The myopathic form is the most common and generally least severe type of CPT II deficiency. It primarily affects the skeletal muscles and can begin showing symptoms anytime from childhood through adulthood.
What triggers a CPT II deficiency metabolic crisis?
Symptoms in the most common form are usually triggered when the body is under stress and needs more energy. Common triggers include prolonged exercise, fasting or skipping meals, high fevers, viral illnesses, and exposure to extreme cold.
Why does my urine turn dark with CPT II deficiency?
Dark, tea-colored, or cola-colored urine is a sign of myoglobinuria. This occurs when muscle tissue rapidly breaks down—a condition called rhabdomyolysis—and releases muscle proteins into the blood, which are then filtered out by your kidneys.
How do the severe infantile and neonatal forms affect children?
The infantile and neonatal forms are much more severe and often affect the liver and heart. They can cause dangerous drops in blood sugar, heart muscle weakness, lethargy, and in the neonatal form, severe structural organ changes shortly after birth.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my/my child's symptoms and genetic results, which of the three subtypes of CPT II deficiency do we have?
  2. 2.Are there specific signs of cardiomyopathy or liver dysfunction we should be monitoring for in our child?
  3. 3.What is the specific 'fever protocol' we should follow to prevent a metabolic crisis during illness?
  4. 4.Does the specific genetic mutation identified (such as S113L) make me/my child more sensitive to temperature or heat?
  5. 5.How can we distinguish between normal muscle soreness from play and the early signs of rhabdomyolysis?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (24)
  1. 1

    Muscle Carnitine Palmitoyltransferase II (CPT II) Deficiency: A Conceptual Approach.

    Joshi PR, Zierz S

    Molecules (Basel, Switzerland) 2020; (25(8)) doi:10.3390/molecules25081784.

    PMID: 32295037
  2. 2

    A case study of lethal neonatal CPT II deficiency: Novel insights from genetic analysis.

    Tran TCM, Ta VT, Bui TB, et al.

    Molecular genetics and metabolism reports 2024; (41()):101170 doi:10.1016/j.ymgmr.2024.101170.

    PMID: 39720737
  3. 3

    Rhabdomyolysis Associated with Recent SARS-COV-2 Infection in a Patient with Carnitine Palmitoyltransferase II Deficiency.

    Rambabova-Bushljetik I, Dzekova-Vidimliski P, Karanfilovski V, et al.

    Prilozi (Makedonska akademija na naukite i umetnostite. Oddelenie za medicinski nauki) 2022; (43(3)):61-66 doi:10.2478/prilozi-2022-0037.

    PMID: 36473042
  4. 4

    Carnitine palmitoyltransferase II deficiency with a focus on newborn screening.

    Tajima G, Hara K, Yuasa M

    Journal of human genetics 2019; (64(2)):87-98 doi:10.1038/s10038-018-0530-z.

    PMID: 30514913
  5. 5

    Recurrent Myalgia since Early Infancy-Misleading Clinical Course in a Child with Carnitine Palmitoyltransferase-II Deficiency.

    Arélin M, Zierz S, Ceglarek U, et al.

    Neuropediatrics 2020; (51(1)):53-56 doi:10.1055/s-0039-1694977.

    PMID: 31541997
  6. 6

    Recurrent rhabdomyolysis caused by carnitine palmitoyltransferase II deficiency, common but under-recognised: Lessons to be learnt.

    Balasubramanian M, Jenkins TM, Kirk RJ, et al.

    Molecular genetics and metabolism reports 2018; (15()):69-70 doi:10.1016/j.ymgmr.2018.02.008.

    PMID: 29744303
  7. 7

    Myopathic Carnitine Palmitoyltransferase II (CPT II) Deficiency: A Rare Cause of Acute Kidney Injury and Cardiomyopathy.

    Castillo E, Medina D, Schoenmann N

    Cureus 2023; (15(10)):e46595 doi:10.7759/cureus.46595.

    PMID: 37933340
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    Adult-onset carnitine palmitoyl transferase II (CPT II) deficiency presenting with rhabdomyolysis and acute kidney injury.

    Akar HT, Yıldız Y, Mutluay R, et al.

    CEN case reports 2024; (13(2)):81-85 doi:10.1007/s13730-023-00804-8.

    PMID: 37341884
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    Phenotype of carnitine palmitoyltransferase II (CPT II) deficiency: A questionnaire-based survey.

    Joshi PR, Deschauer M, Zierz S

    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 2019; (59()):32-36 doi:10.1016/j.jocn.2018.11.023.

    PMID: 30455135
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    Cause of recurrent rhabdomyolysis, carnitine palmitoyltransferase II deficiency and novel pathogenic mutation.

    Çakar NE, Gör Z, Yeşil G

    Ideggyogyaszati szemle 2021; (74(3-4)):135-138 doi:10.18071/isz.74.0135.

    PMID: 33938664
  11. 11

    Stabilization of the thermolabile variant S113L of carnitine palmitoyltransferase II.

    Motlagh L, Golbik R, Sippl W, Zierz S

    Neurology. Genetics 2016; (2(2)):e53 doi:10.1212/NXG.0000000000000053.

    PMID: 27123472
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    Muscle Carnitine Palmitoyltransferase II Deficiency: A Review of Enzymatic Controversy and Clinical Features.

    Lehmann D, Motlagh L, Robaa D, Zierz S

    International journal of molecular sciences 2017; (18(1)) doi:10.3390/ijms18010082.

    PMID: 28054946
  13. 13

    Successful orthotopic heart transplantation in CPTII deficiency.

    Arnold GL, Yester J, McCracken E, et al.

    Molecular genetics and metabolism 2021; (133(2)):182-184 doi:10.1016/j.ymgme.2021.04.005.

    PMID: 34020866
  14. 14

    A Case of Carnitine Palmitoyltransferase II Deficiency in Bahrain With a Novel Mutation.

    Alsahlawi Z, Fadhul Z, Mahmood A, et al.

    Cureus 2022; (14(6)):e26043 doi:10.7759/cureus.26043.

    PMID: 35859960
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    Neonatal Carnitine Palmitoyltransferase II Deficiency: A Lethal Entity.

    Malik S, Paldiwal AA, Korday CS, Jadhav SS

    Journal of clinical and diagnostic research : JCDR 2015; (9(10)):SD01-2 doi:10.7860/JCDR/2015/13600.6560.

    PMID: 26557586
  16. 16

    Newborn Screening with (C16 + C18:1)/C2 and C14/C3 for Carnitine Palmitoyltransferase II Deficiency throughout Japan Has Revealed C12/C0 as an Index of Higher Sensitivity and Specificity.

    Tajima G, Hara K, Tsumura M, et al.

    International journal of neonatal screening 2023; (9(4)) doi:10.3390/ijns9040062.

    PMID: 37987475
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    Metabolic cardiomyopathies: untangling clinical heterogeneity with human stem-cell derived models.

    Passadouro AS, Balfoort BM, Langeveld M, et al.

    EMBO molecular medicine 2025; (17(11)):2853-2874 doi:10.1038/s44321-025-00313-4.

    PMID: 40983718
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    A surviving 24-month-old patient with neonatal-onset carnitine palmitoyltransferase II deficiency.

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    Molecular genetics and metabolism reports 2017; (11()):69-71 doi:10.1016/j.ymgmr.2017.04.010.

    PMID: 28529889
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    Carnitine palmitoyltransferase II (CPT II) deficiency responsible for refractory cardiac arrhythmias, acute multiorgan failure and early fatal outcome.

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    Sudden infant death from neonate carnitine palmitoyl transferase II deficiency.

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    Do renal and cardiac malformations in the fetus signal carnitine palmitoyltransferase II deficiency? A rare lethal fatty acid oxidation defect.

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    BMJ case reports 2022; (15(12)) doi:10.1136/bcr-2022-251321.

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    Infantile onset carnitine palmitoyltransferase 2 deficiency: Cortical polymicrogyria, schizencephaly, and gray matter heterotopias in an adolescent with normal development.

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This page explains the subtypes and symptoms of CPT II deficiency for informational purposes only. Always consult your healthcare provider or metabolic specialist for diagnosis and personalized medical advice.

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